Triethylamine hydrochloride → 6-Chloro-3-(2,6-difluorophenyl)-7-(1,1-dimethylethyl)-1,2,4-triazolo[4,3-b]pyridazine

HRID 2301337

Reaction equation

HRID 2301337 reaction equation
[Cl:1][C:2]1[N:3]=[N:4][C:5](Cl)=[CH:6][C:7]=1[C:8]([CH3:11])([CH3:10])[CH3:9].[F:13][C:14]1[CH:23]=[CH:22][CH:21]=[C:20]([F:24])[C:15]=1[C:16]([NH:18][NH2:19])=O.Cl.C(N(CC)CC)C>O1CCOCC1>[Cl:1][C:2]1[C:7]([C:8]([CH3:11])([CH3:10])[CH3:9])=[CH:6][C:5]2[N:4]([C:16]([C:15]3[C:20]([F:24])=[CH:21][CH:22]=[CH:23][C:14]=3[F:13])=[N:18][N:19]=2)[N:3]=1

Participants

5

Reactant 3

HCID 11130Triethylamine hydrochlorideHCID 898464-tert-Butyl-3,6-dichloropyridazineHCID 6764492,6-Difluorobenzhydrazide

Product 1

HCID 183724156-Chloro-3-(2,6-difluorophenyl)-7-(1,1-dimethylethyl)-1,2,4-triazolo[4,3-b]pyridazineYield 13.3%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Procedure

A mixture of 3,6-dichloro-4-(1,1-dimethylethyl)pyridazine (2 g, 9.75 mmol), 2,6-difluorobenzoic acid hydrazide (2.52 g, 14.6 mmol) (WO 95/24403) and triethylamine hydrochloride (2.01 g, 14.6 mmol) in 1,4-dioxane (10 ml) was stirred and heated at reflux for 3.5 days. Upon cooling, the volatiles were removed in vacuo and the residue was triturated with dichloromethane. Any undissolved solid was removed by filtration. The residue was purified by chromatography on silica gel eluting with 0%→25% ethyl acetate in dichloromethane to give the required product (0.42 g). Data for the title compound: 1H NMR (250 MHz, CDCl3) δ1.57 (9H, s), 7.09-7.16 (2H, m), 7.51-7.63 (1H, m), 8.19 (1H, s); MS (ES30) m/e 323 (MH+.

Workup

  1. temperatureheated
  2. temperatureat reflux for 3.5 days
  3. temperatureUpon cooling
  4. customthe volatiles were removed in vacuo
  5. customthe residue was triturated with dichloromethane
  6. customAny undissolved solid was removed by filtration
  7. customThe residue was purified by chromatography on silica gel eluting with 0%→25% ethyl acetate in dichloromethane

Sources & evidence

ORD record
ord-34c2f76c0c3849799ce74e5dab82164e
Source dataset
uspto-grants-2002_12
Patent number
US06500828B1

Linked notes

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